Target: ROS

So that's the story--so far--on treating brain ischemia by going after the initiating events, events that unleash the Four Horsemen. But perhaps your plan took into account the difficulty of getting to the patient's neurons before the Horsemen got out. Perhaps you decided to go after one of the Horsemen instead. Perhaps you decided to go after oxidative stress.

You're not the first to think of this. It ain't brain surgery. We've seen how damaging ROS can be during reperfusion, and how oxidative stress has the potential to strengthen other Horsemen. It's easy to postulate that supressing oxidative stress might not only limit direct oxidative damage to macromolecules, but could also dampen apoptosis and possibly even translation inhibition.

And believe me, this has been a very active area of research. Free radical scavenging agents like PBN, NXY-059, deferoxamine, trilizade and many others have been subjects of intense scrutiny.

Figure. PBN, a classic free radical "spin trap."

Here's the problem with free radical scavengers: they don't work. Although you can definitely make rats and gerbils better with anti-ROS modalities, they don't seem to cut the mustard in humans. Most recently, the "spin-trap" NXY-059, which had shown great promise in a phase III clinical trial, flamed out in subsequent studies.